ABCMdb

PMID: 23934925

Rab A, Rowe SM, Raju SV, Bebok Z, Matalon S, Collawn JF
Cigarette smoke and CFTR: implications in the pathogenesis of COPD.
Am J Physiol Lung Cell Mol Physiol. 2013 Oct 15;305(8):L530-41. doi: 10.1152/ajplung.00039.2013. Epub 2013 Aug 9., [PubMed]

Sentences

No. Mutations Sentence Comment

68 ABCC7 p.Gly551Asp Similarly, another mutation, G551D, yields a protein that is transported to the cell surface but is unable to transport anions and thus has a channel-gating defect. Login to comment 69 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Only six other mutations have a frequency of greater than 1% in the CF population (G542X, W1282X, G551D, 621 af9; G&#a1;T, N1303K, and R553X) (157). Login to comment 71 ABCC7 p.Gly551Asp Although there is no cure for CF, current therapies, particularly with regard to the gating mutants (G551D and others), are highly effective toward augmenting CFTR function and improving clinical outcome (5, 48, 120, 151). Login to comment 123 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Gly542* Alternative approaches have included high-throughput screens to identify small molecules that promote either 1) F508del CFTR rescue and delivery to the cell surface (108), 2) read-through of premature stop mutations to override nonsense mutations and help translation to produce full-length proteins (e.g., G542X, W1282X, etc.) (160), or 3) potentiation of channel-gating mutations such as G551D (151). Login to comment 183 ABCC7 p.Gly551Asp The discovery of potent CFTR activators such as ivacaftor for CF patients with CFTR mutations leading to functional defects such as G551D and the observed CFTR dysfunction seen in COPD patients prompted some investigators to test the compound for both disorders (138). Login to comment 211 ABCC7 p.Gly551Asp demonstrated that wild-type CFTR expression could also attenuate proinflammatory cytokine secretion, whereas G551D CFTR could not, indicating that chloride channel activity was necessary for this effect (152). Login to comment